Дисертації з теми "Bone inhibition"
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Hussein, Hayam. "Cathepsin K Inhibition In Bone And Bone Marrow In Horses." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1449218489.
Повний текст джерелаBui, Lynn. "Inhibition of System Xc⁻ Reduces Cancer-Induced Bone Pain." Thesis, The University of Arizona, 2014. http://hdl.handle.net/10150/321599.
Повний текст джерелаPappalardo, Angela. "Defining the role of γδ cells in bone loss associated with chronic inflammation". Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=203414.
Повний текст джерелаAl-Masri, Maher. "Limitations of bone formation in oral implantology : inhibition of osteoblast functions by gingival tissues." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/356.
Повний текст джерелаSukhtankar, Devki, Alec Okun, Anupama Chandramouli, Mark Nelson, Todd Vanderah, Anne Cress, Frank Porreca, and Tamara King. "Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain." BioMed Central, 2011. http://hdl.handle.net/10150/610213.
Повний текст джерелаYoshioka, Yumiko. "Differential effects of inhibition of bone morphogenetic protein (BMP) signalling on T-cell activation and differentiation." Kyoto University, 2012. http://hdl.handle.net/2433/157448.
Повний текст джерелаWickman, Sanna. "Aromatase inhibition in boys with delayed puberty effects on growth, maturation, bone, serum lipids, and insulin." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/wickman/.
Повний текст джерелаDai, Rongchen. "Development of an osteoclast-targeted cathespin K inhibitor for postmenopausal osteoporosis : in vitro evaluation and pharmacokinetic profile." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/840.
Повний текст джерелаNolan, Kristof T. "Insights into the Molecular Determinants Required for DAN-family Mediated Inhibition of BMP Signaling." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1468335666.
Повний текст джерелаAlbishi, Waleed. "Inhibition of fibroblast growth factor receptor 3 (FGFR3) signalling to accelerate bone formation during distraction osteogenesis of mice tibiae." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121465.
Повний текст джерелаL'ostéogénèse par distraction (Distraction Osteogenesis, DO) est une technique chirurgicale largement utilisée pour le traitement des anomalies de la longueur des membres, des malformations, des fractures non-union, et de la perte osseuse suivant un traumatisme. La technique consiste à effectuer une ostéotomie puis à éloigner progressivement les deux segments osseux à l'aide d'un fixateur externe. Du nouveau tissu osseux se forme progressivement dans l'espace créé par la traction. Bien que montrant un taux de succès élevé, un des désavantages de cette technique est la longue période de temps où le fixateur externe doit être maintenu en place afin que l'os nouvellement formé se consolide. Cette période prolongée peut entraîner de nombreuses complications d'ordre social, psychologique ou médical. Des résultats récents de notre laboratoire montrent que l'absence de signalisation par le récepteur 3 des facteurs de croissance fibroblastiques (Fibroblast Growth Factor Receptor 3, FGFR3) au cours de la DO conduit à une augmentation de la formation osseuse chez les souris déficientes en FGFR3. Nous avons donc émis l'hypothèse que le blocage de la voie signalétique FGFR3 chez des souris de type sauvage pourrait être efficace afin d'augmenter la formation osseuse au cours de la DO. Afin de bloquer cette voie signalétique, nous avons utilisé un inhibiteur synthétique, PD173074, ou des anticorps anti-FGFR3. Des souris C57Bl/6 de type sauvage agée de 2 mois et divisée en 5 groupes. Les souris ont subi une ostéotomiechirurgicale et l'installation du fixateur externe (appareil de distraction). Après une période de récupération de 5 jours, la distraction a été amorcée (0,2 mm/12 heures pendant 12 jours). Les animaux ont été sacrifiés au jour 33 post-chirurgie (mi-consolidation). À l'aide de la tomographie haute résolution assistée par ordinateur (micro-computedtomography, μCT), nous avons comparé la formation osseuse dans l'espace créé par la traction entre le groupe contrôle (recevant seulement le véhicule) et les groupes traités avec une des trois doses croissantes d'inhibiteur ou avec l'anticorps anti-FGFR3. Nos résultats montrent une tendance dose-dépendante à l'augmentation de la formation osseuse chez les souris recevant l'inhibiteur, par rapport aux souris non traitées. Cette étude pilote est un jalon important dans la recherche translationnellevisant à accélérer la formation osseuse au cours de l'ostéogénèse par distraction.
Tan, Jamie We-Yin. "The investigation of RANKL TNF-like core domain by truncation mutation." University of Western Australia. School of Surgery and Pathology, 2003. http://theses.library.uwa.edu.au/adt-WU2004.0032.
Повний текст джерелаTeufel, Stefan [Verfasser], and Georg [Akademischer Betreuer] Schett. "Inhibition of bone remodeling by anti-resorptive drugs displaces the plasma cell niche into the spleen / Stefan Teufel. Gutachter: Georg Schett." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2015. http://d-nb.info/1076120601/34.
Повний текст джерелаHara, Toshiaki, Nanako Ogasawara, Hidetoshi Akimoto, Osamu Takikawa, Rie Hiramatsu, Tsutomu Kawabe, Ken-ichi Isobe, Fumihiko Nagase, and 文彦 長瀬. "High-affinity uptake of kynurenine and nitric oxide-mediated inhibition of indoleamine 2,3-dioxygenase in bone marrow-derived myeloid dendritic cells." Elsevier, 2008. http://hdl.handle.net/2237/11381.
Повний текст джерелаGuimarÃes, Mariana Vasconcelos. "Matricaria recutita prevents ligature-induced osteoclastic alveolar bone loss induced in rats via inhibition of TNFa and IL-1β cytokines." Universidade Federal do CearÃ, 2014. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=14266.
Повний текст джерелаPeriodontitis is an immunoinflammatory disease in that the involvement of chemical mediators culminates in destruction of alveolar bone. Long recognized regarding its pathogenesis, however, frequently some patients do not respond insatisfactorily to conventional treatments, which makes pharmacological alternatives are sought. In this context, Matricaria recutita (MTR), known as chamomile, stands out in the literature for its anti-inflammatory and a variety of constituents, especially apigenin (APG) flavonoid. Thus, the present study evaluated the involvement of cytokines in the anti-inflammatory and antiresorptive activities of MTR in alveolar bone resorption (ABR) induced by ligature in rats. For this, we used the dry extract of MTR (apigenin content 128.5Â0.99 mg/g). The ABR was induced in 90 wistar rats (199.3 Â 3.2 g) by ligation (nylon 3.0) of 2Â upper left molar, and contralateral was used as control. The rats received v.o. Tween 80 (TW) or MTR (10, 30 and 90 mg/kg) daily until 11 d, when they were killed. The hemiarcadas were processed for macroscopic (mm2) or histometric, histological and immunohistochemical analyzes for the ligand of the receptor activator of nuclear factor kappa B (RANKL), osteoprotegerin (OPG) and tartrate-resistant acid phosphatase (TRAP). Blood samples were collected for measurement of bone alkaline phosphatase (BALP), while the gingival tissue was used for measuring of mieloperoxidase activity (MPO; mg/g) and of tumor necrosis factor-alpha (TNF-a) and interleukin-1β (IL-1β) levels (pg/mg) by ELISA. Systemically, serum bone alkaline phosphatase (BALP), AST/ALT, urea and creatinine, and white blood count were made, and we evaluated of macroscopic aspects of liver, kidneys and spleen, in addition to variation in body mass. Was set at p <0.05 (#) for Normal, (*) for TW and () for MTR 10 mg/kg; Ethical aspects: the Ethics Committee for Animal Use-UFC 70/13. It was found that ligation for 11 days caused intense ABR with furcation lesion pronounced, resorption of alveolar bone and cementum in the region between the first and second molars, reduction of serum BALP, intense leukocyte infiltrate in the periodontium these animals, increasing significant MPO, TNF-, IL-1β in challenged area underlying gingival tissue, and increased to RANKL and TRAP immunostaining, and reduced to OPG. Systemically, there was leukocytosis with a predominance of mononuclear cells. No major changes in organs and weight of animals were observed. MTR prevented, significantly, the ligature-induced ABR [TW=5.5Â0.2; MTR (10)=4.4Â0.1*; (30)=2.9Â0.1*; (90)=2.8Â0*], corroborating the reduction of furcation lesions [Normal=10.4Â0.8; TW=137.4Â23.3#; MTR (90)=81.0Â9.6*#] and the preservation of the alveolar bone and cementum [(Normal=0(0-0); TW=3(1-3)#, MTR (90)=1(1-3)#*] compared to the TW group while no bone anabolic activity was showed because MTR dit not prevent the reduction of serum BALP induced by ligature [Normal=99.4Â3.4; TW=61.3Â2.6#; MTR (10)=70.6Â3.6#; (30)=74.5Â3.7#; (90)=78.5Â2.8#); p>0.05]. However, MTR significantly prevented the leukocyte infiltration and the increase of MPO activity [Normal=3.6Â0.5; TW=9.4Â0.9#; MTR (10)=10.2Â3.3; (30)=4.5Â0.8*; (90)=4.2Â0.7*], of TNF-a [Normal=0.2Â0; TW=1.2Â0.2#; MTR (10)=0.4Â0.2*; (30)=0.2Â0.1*; (90)=0.1Â0*] and of IL-1β [Normal=1.5Â0.3; TW=8.0Â1.4#; MTR (10)=8.9Â1.9#; (30)=1.8Â1.0*; (90)=1.5Â0.9*] levels caused by ligature, and reduced immunostaining for RANKL and TRAP, and increased for OPG, comparing to TW group. Additionally, MTR prevented the leukocytosis caused by ligation and did not alter liver, kidney, spleen conditions or the variation of body mass. In short, the MTR prevented the ABR by reducing TNF-a and IL-1β, thus preventing the osteoclast activation due RANK-RANKL-OPG axis, without interfering with bone anabolism.
A periodontite à uma doenÃa imunoinflamatÃria onde a participaÃÃo de mediadores quÃmicos culmina em destruiÃÃo de osso alveolar. Muito se reconhece a respeito de sua patogÃnese, contudo, frequentemente alguns pacientes respondem de forma insatisfatÃria aos tratamentos convencionais, o que faz com que alternativas farmacolÃgicas sejam buscadas. Neste contexto, a Matricaria recutita (MTR), conhecida como camomila, destaca-se na literatura por sua propriedade anti-inflamatÃria e sua variedade de constituintes, especialmente o flavonoide apigenina. Assim, o presente estudo avaliou a participaÃÃo de citocinas nas atividades anti-inflamatÃria e antirreabsortiva da MTR na reabsorÃÃo Ãssea alveolar (POA) induzida por ligadura em ratos. Para isso, utilizou-se extrato seco de MTR (teor de apigenina de 128,5Â0,99 mg/g). A POA foi induzida em 90 ratos Wistar (199,3Â3,2 g) por ligadura (nÃilon 3.0) do 2 molar superior esquerdo, e contralateral como controle. Os ratos receberam v.o. Tween 80 (TW) ou MTR (10, 30 e 90 mg/kg) diariamente atà o 11 d, quando foram mortos. As hemiarcadas foram processadas para macroscopia (mm2) ou para anÃlises histomÃtrica, histolÃgica e imunohistoquÃmica para o ligante do receptor ativador do fator nuclear kappa-B (RANKL), a osteoprotegerina (OPG) e a fosfatase Ãcida resistente ao tartarato (TRAP). Amostras de sangue foram coletadas para dosagem de fosfatase alcalina Ãssea (FAO), enquanto que o tecido gengival foi utilizado para a dosagem da atividade de mieloperoxidase (MPO; mg/g), do fator de necrose tumoral-alfa (TNF-a) e da interleucina-1β (IL-1β) (pg/mg) por ELISA. Sistemicamente, foram feitas dosagens sÃricas AST/ALT, ureia e creatinina, avaliados leucograma, os aspectos macroscÃpicos de fÃgado, rins e baÃo, alÃm da variaÃÃo de massa corpÃrea. Considerou-se p<0,05 (#) para Normais, (*) para TW e () para MTR 10 mg/kg; Aspectos Ãticos: ComissÃo de Ãtica para Uso de Animais-UFC n 70/13. Verificou-se que a ligadura durante 11 dias causou intensa POA, com lesÃo pronunciada de furca e reabsorÃÃo de osso alveolar e cemento na regiÃo entre o primeiro e segundo molares, reduÃÃo dos nÃveis sÃricos de FAO, intenso infiltrado leucocitÃrio no periodonto destes animais, aumento significante de MPO, de TNF-a, de IL-1β no tecido gengival subjacente à Ãrea desafiada, alÃm de imunomarcaÃÃo aumentada para RANKL e TRAP, e reduzida para OPG. Sistemicamente, observou-se leucocitose com predomÃnio de mononucleares. NÃo foram observadas alteraÃÃes importantes de ÃrgÃos e peso dos animais. MTR foi capaz de prevenir, de forma significante, a POA induzida por ligadura [TW=5,5Â0,2; MTR (10)=4,4Â0,1*; (30)=2,9Â0,1*; (90)=2,8Â0*], sendo corroborada pela reduÃÃo das lesÃes de furca [Normal=10,4Â0,8; TW=137,4Â23,3#; MTR (90)=81,0Â9,6#*] e preservaÃÃo de osso alveolar e cemento [(Normal=0(0-0); TW=3(1-3)#; MTR (90)=1(1-3)#*] em comparaÃÃo ao grupo TW, embora nÃo demonstrou atividade anabÃlica Ãssea por nÃo prevenir a reduÃÃo dos nÃveis sÃricos de FAO induzida pela ligadura [Normal=99,4Â3,4; TW=61,3Â2,6#; MTR (10)=70,6Â3,6#; (30)=74,5Â3,7#; (90)=78,5Â2,8#); p>0,05]. Entretanto, MTR preveniu significantemente o infiltrado leucocitÃrio e o aumento da atividade de MPO [Normal=3,6Â0,5; TW=9,4Â0,9#; MTR (10)=10,2Â3,3; (30)=4,5Â0,8*; (90)=4,2Â0,7*], dos nÃveis de TNF-a [Normal=0,2Â0; TW=1,2Â0,2#; MTR (10)=0,4Â0,2*; (30)=0,2Â0,1*; (90)=0,1Â0*] e de IL-1β [Normal=1,5Â0,3; TW=8,0Â1,4#; MTR (10)=8,9Â1,9#; (30)=1,8Â1,0*; (90)=1,5Â0,9*], proporcionando imunomarcaÃÃo reduzida para RANKL e TRAP, e aumentada para OPG, em comparaÃÃo ao grupo TW. Adicionalmente, a MTR preveniu a leucocitose causada pela ligadura e nÃo alterou as condiÃÃes hepÃticas, renais, esplÃnicas e a variaÃÃo de massa corpÃrea. Em suma, a MTR preveniu a POA via reduÃÃo de TNF-a e IL-1β, prevenindo, assim, a ativaÃÃo osteoclÃstica decorrente do eixo RANK-RANKL-OPG, sem interferir no anabolismo Ãsseo.
Olson, Janelle Ann. "Natural killer cell tissu-specific trafficking and direct inhibition of graft-versus-host disease-inducing T cells in bone marrow transplantation /." May be available electronically:, 2009. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Повний текст джерелаPersson, Per-Erik. "Heterotopic Ossification : Clinical and Experimental Studies on Risk Factors, Etiology and Inhibition by Non-steroidal Anti-inflammatory Drugs." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3908.
Повний текст джерелаYu, Vionnie Wing Chi. "Factor inhibiting ATF4-mediated transcription is a novel leucine zipper transcriptional repressor that regulates bone mass." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103311.
Повний текст джерелаTwitty, Anne. "The expression of tissue inhibitor of metalloproteinase during the early stages of bone graft healing." Thesis, Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21804023.
Повний текст джерелаLi, Qianfeng, and 李乾凤. "Vastatin, a novel angiogenesis inhibitor, retards condylar bone growthin vivo." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42181951.
Повний текст джерелаLi, Qianfeng. "Vastatin, a novel angiogenesis inhibitor, retards condylar bone growth in vivo." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42181951.
Повний текст джерелаUmaretiya, Puja Jagdish. "Cathepsin Inhibitor, VBY-825, Attenuates Bone Cancer Induced Pain in Mice." Thesis, The University of Arizona, 2011. http://hdl.handle.net/10150/145000.
Повний текст джерелаClayton, Nicholas J. "Bromodomain and Extraterminal Domain (BET) Inhibitor RVX-208 Ameliorates Periodontal Bone Loss." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5380.
Повний текст джерелаLogan, John Gordon. "Targeting bone-microenvironment-tumour cell interactions : IGF-1 receptor kinase inhibitors." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/8184.
Повний текст джерелаOndoua, Alysia. "Novel Mechanisms and Therapeutics in the Treatment for Cancer-Induced Bone Pain." Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/293445.
Повний текст джерелаNikolich-Zugich, Tuana. "Multivalent Cathepsin Inhibitor, VBY-825, Attenuates Breast-Induced Bone Cancer Remodelling and Pain." Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/297716.
Повний текст джерелаKaipatur, Neelambar. ""Inhibition of mineralization in bones and teeth following ectopic expression of matrix Gla protein"." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82260.
Повний текст джерелаBjelic, Sinisa. "Molecular Simulation of Enzyme Catalysis and Inhibition." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7468.
Повний текст джерелаPan, Beiqing. "Molecular and cellular studies of zoledronic acid : a potent inhibitor of multiple myeloma-induced osteolysis." Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09MSM/09msmp187.pdf.
Повний текст джерелаAllen, James Henry. "A comparison of the enamel demineralization inhibition and shear bond strength of two orthodontic resins." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2009m/allen.pdf.
Повний текст джерелаPabin, Zarina Maria. "Effects of Duration of Proton Pump Inhibitor (PPI) Therapy on Markers of Bone Health in Men and Postmenopausal Women." BYU ScholarsArchive, 2010. https://scholarsarchive.byu.edu/etd/2580.
Повний текст джерелаRen, Zhongyuan. "Small molecules regulated bone resorption and enzyme activity in osseous cells." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10291/document.
Повний текст джерелаCathepsin K is among the most potent mammalian collagenase, capable of cleaving the triple helix in type-I collagen. We developed a series of azanitriles (CKI-8 and CKI-13) which are inhibitors of cathepsin K. CKI-8 (an isomer of CKI-13) and CKI-13 did not induce significant toxicity on osteoblasts Saos-2 and RAW 264.7 cells up to 1000 nM, while they were not toxic on mature osteoclasts up to 100 nM. Commercial E64 inhibitor was not toxic in primary osteoclast cells up to 1000 nM. CKI-8 did not affect alkaline phosphatase activity as well the mineralization induced by Saos-2 cells and by primary osteoblasts. CKI-13 decreased by 35% the mineralization induced by Saos-2 cells while it did not on mineralization induced by primary osteoblasts. Addition of CKI-13 decreased alkaline phosphatase activity by around 20% (Saos-2 cells) and 45% (primary osteoblasts). Bone resorption on bovine slices decreased significantly with 10 nM of CKI-13, with 100 nM of CKI-8 and commercial inhibitor E64. Our findings indicated that CKI-8 and CKI-13 inhibited bone resorption and affected the mobility of osteoclast. To monitor directly the PPi hydrolytic activity by alkaline phosphatase, we developed an infrared (IR) assay taking the advantage to use natural substrate under physiological pH in matrix vesicles and in living cells. PPi band located at 1107 cm-1 (∑= 2158 ± 211 M-1.cm-1) and Pi bands located at 1076 cm-1 (∑= 1346 ± 116 M-1.cm-1) and at 991 cm-1 (∑= 493 ± 49 M-1.cm-1) served to measure the substrate and the product concentrations
Lee, Joanne Sung Yun. "The effect of Batimastat, a matrix metalloproteinase inhibitor, on experimental bone metastasis in an animal model." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0014/MQ32935.pdf.
Повний текст джерелаDickson, Iain Gordon. "73-deoxychondropsin A : a novel inhibitor of bone resorption sourced from a Great Barrier Reef sponge." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/73deoxychondropsin-a(ed6d432a-14a1-4836-b02a-04cf14391c51).html.
Повний текст джерелаTaylor, Alan. "The role of leukaemia inhibitory factor and a leukaemic associated inhibitor in the control of the proliferation of haematopoietic stem cells." Thesis, University of St Andrews, 1996. http://hdl.handle.net/10023/14962.
Повний текст джерелаGeraldeli, Gizele M. R. "Microtensile bond strength after environmental challenge of peak SE with proteolytic inhibitor." Thesis, University of Iowa, 2012. https://ir.uiowa.edu/etd/2874.
Повний текст джерелаGhilardi, Joseph, Katie Freeman, Juan Jimenez-Andrade, William Mantyh, Aaron Bloom, Michael Kuskowski, and Patrick Mantyh. "Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain." BioMed Central, 2010. http://hdl.handle.net/10150/610212.
Повний текст джерелаKupselaitis, Kurt. "Evaluation of Strand to Grout Bond in Post-Tensioned Tendons with Corrosion Inhibiting Penetrants." Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7834.
Повний текст джерелаLawlor, Liam Michael. "The effect of HDAC inhibitor MI192 on stem cell behaviour : the potential of utilising MI192 for bone tissue engineering." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/13512/.
Повний текст джерелаTauer, Josephine Tabea. "Auswirkungen einer Langzeitexposition mit den Tyrosinkinase-Inhibitoren Imatinib, Dasatinib und Bosutinib auf das Skelett und weitere Organsysteme im neu etablierten Tiermodell der juvenilen Ratte." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-118848.
Повний текст джерелаBackground: Since its approval in 2001 the tyrosine kinase inhibitor (TKI) imatinib has revolutionized the therapy of chronic myeloid leukaemia (CML). Imatinib inhibits the constitutively active tyrosine kinase (TK) BCR-ABL causing the increased proliferation of the leukemic cells and the progress of CML. According to improved survival rates imatinib has been licensed as frontline therapy also for paediatric CML in 2003. However, due to point mutations or structural changes within the BCR-ABL fusion protein resistance to imatinib occurs. Therefore 2nd and 3rd generation TKI like dasatinib and bosutinib have been developed. Beside BCR-ABL, Imatinib exerts also off-target effects on further TKs like c-KIT, PDGF-R, c-FMS which are involved in bone metabolism. Stimulation of the receptor c-FMS leads to the differentiation of monocytic progenitors to bone resorbing osteoclasts. In addition, the development of bone forming osteoblasts underlies specific signalling cascades involving PDGF-R and c-Abl. As a side effect of TKI therapy these specific signalling cascades are inhibited impairing bone remodelling by reducing the development and functional activity of osteoclasts. Simultaneously osteoblasts’ differentiation is promoted while their proliferation is inhibited. This dysbalance of bone formation and resorption results in altered endocrinological serum markers of the calcium homeostasis, increased bone mineralization, and increased trabecular bone density in adult CML patients. In contrast paediatric CML patients show longitudinal growth retardations under imatinib therapy, however, the detailed action of imatinib on the growing bone is not clarified yet. Additionally, it is unclear if 2nd and 3rd generation TKI will also disturb bone metabolism in paediatric CML patients. Based on an effective treatment strategy in adult CML patients, it is also questioned if intermittent TKI treatment (one month “on”, one month “off”) could minimise side effects on the bone without impairing CML therapy. On this background a rodent model was established to study side effects of TKI treatment on bone metabolism. Juvenile growing rats where exposed from prepubertal age till adolescence continuously or intermittently to imatinib, dasatinib, and bosutinib and the effects on the growing skeleton were analysed. Methods: Four weeks old male Wistar rats were chronically exposed to varying concentrations of one of the three TKIs via the drinking water for 10 weeks. Besides untreated controls a standard dosage group and a high dosage group (equalling the twofold standard dose) received every TKI continuously, while an additional group received the high dosage TKI in an intermittent fashion (3 days per week: “on” TKI; 4 days water without TKI). The concentrations applied were 1 mM and 2 mM for imatinib and 50 µM and 100 µM each for dasatinib and bosutinib, respectively. After 2 weeks (prepubertal), 4 weeks (pubertal stage), and 10 weeks (postpubertal) of exposure, respectively, animals were sacrificed and long bones, lumbar vertebra and blood were isolated. To evaluate bone metabolism the following parameters were analysed: bone length, bone mineral density (BMD) by pQCT, trabecular structure by µCT, bone strength by 3-point bending test, and endocrinological parameters by ELISA. Additionally, serum levels of TKIs were investigated. Results: In comparison to controls no alterations of exposed animals’ bodyweight, overall development and social behaviour were observed. Continuous exposure of imatinib and dasatinib led dose dependently to reduced femoral and tibial length. No such effect was observed under bosutinib. Intermitted exposure of high-dose TKIs resulted in reduced effects on femoral and tibial length identical to the effect observed in groups receiving just standard dose. Furthermore, exposure of imatinib and dasatinib lowered femoral and tibial trabecular BMD prepubertally. Rats receiving high dose imatinib showed reduced femoral and tibial trabecular BMD at pubertal stage, while this effect was not observed under dasatinib and bosutinib exposure. Postpubertally, femoral and tibial trabecular BMD of all exposed groups did not differ from controls. Femoral and tibial cortical BMD and cortical thickness were not affected by TKI exposure. However, under high dose imatinib exposure femoral mechanical breaking strength was reduced postpubertally. In vertebra the height was reduced under imatinib exposure pubertally and postpubertally, while the total and cortical BMD were increased prepubertally and trabecular BMD tended to be reduced. Cortical thickness was not affected by any TKI tested. Dasatinib and bosutinib exhibited no effect on the height of the vertebra but trabecular BMD tended to be reduced. The serum bone resorption marker ‘tartrate resistant acidic phosphatase’ (TRAP) was found reduced under continuous exposure of high dose of imatinib at all time points tested. Postpubertally, the same effect was detected after standard and high dosage of bosutinib. The bone formation marker osteocalcin was reduced in all groups and at all time points tested under imatinib exposure, whereas no such effect was observed for dasatinib and bosutinib. Serum bone related hormone markers (growth hormone (GH) and parathyroid hormone (PTH)) revealed under imatinib exposure increased GH levels pubertally whereas PTH was reduced pre- und pubertally. During dasatinib exposure GH levels were elevated pubertally and PTH levels were increased prepubertally. Postpubertally, both parameters normalised again under imatinib and dasatinib exposure. During bosutinib exposure reduced PTH levels were detected postpubertally only. Intermitted TKI exposure resulted in catch-up growth and partial normalisation of bone specific serum parameters. As major unexpected side effect during exposure increasing heart weights could be observed under long-time imatinib and dasatinib exposure. No clinical changes were observed under imatinib, whereas dasatinib led to cardiac insufficiency leading to death of one animal. Bosutinib showed no additional macrospathologic assessable side effects. To date no cardiac side effects were published in paediatric patients under prolonged TKI therapy. Conclusion: The established juvenile rat model is appropriate to examine side effects of long-term TKI exposure on the growing bone. Published longitudinal growth retardation in children and adolescents under imatinib treatment could be unequivocally mimicked in this rat model. Due to not yet available clinical experience with dasatinib in paediatric patients, this model predicts that dasatinib alters bone metabolism like imatinib whereas bosutinib shows less detectable effects. Intermitted TKI treatment may reduce side effects on the growing bone and therefore could represent a new opportunity of TKI therapy for paediatric patients. Summing up, TKI long-term exposure in this juvenile rat model challenges physicians to diligently monitor bone metabolism in not outgrown paediatric patients during long-term TKI treatment and additionally assess cardiac side effects under dasatinib exposure
Valkealahti, M. (Maarit). "The effects of bisphosphonates and COX-2 inhibitors on the bone remodelling unit." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514288548.
Повний текст джерелаTiivistelmä Läpi elämän luustossa tapahtuu uudelleenmuotoutumista, remodelaatiota, jonka seurauksena luu pystyy paremmin vastaamaan muuttuneisiin kuormitusolosuhteisiin. Remodelaatioprosessi on hyvin haavoittuvainen murtuman luutumisen aikana sekä proteesin kiinnittyessä ympäröivään luuhun. Luun remodelaatioon osallistuvat kasvutekijät, sytokiinit ja entsyymit, jotka puolestaan ovat välttämättömiä osteoblastien ja osteoklastien erilaistumiselle. Monet lääkeaineet voivat yllättävällä tavalla vahingoittaa tätä herkkää remodelaatiosysteemiä. Kipulääkkeet, kuten syklo-oksygenaasi (COX) estäjät, voivat häiritä murtuman luutumista aikaisempien eläintöiden ja muutamien retrospektiivisten potilastutkimusten mukaan. Lisäksi bisfosfonaatit, joiden päävaikutuskohde on luuta hajoittava osteoklasti, voisivat olla lupaavia lääkkeitä myös parantamaan proteesia ympäröivän luun laatua ja siten estämään aseptista implantin irtoamista. Tutkimuksen yhtenä tarkoituksena oli selvittää klodronaatin, ensimmäisen polven typpi-ryhmää sisältämättömän bisfosfonaatin tarkka vaikutusmekanismi. Viljelemällä ihmisen luuytimen kantasoluja indometasiinia, parekoksibia tai spesifistä COX-2 estäjää NS 398:a, sisältävässä kasvatusliuoksessa selvitettiin COX-entsyymin merkitys osteoblastien erilaistumiselle. Liposomien sisälle pakattua klodronaatin metaboliittia (AppCCl2p) käytettiin tutkittaessa millä vaikutusmekanismilla klodronaatti aiheuttaa osteoklastien apoptoosin. Bisfosfonaattien; klodronaatin, pamidronaatin ja tsoledronaatin vaikutusta osteoklastien ja osteoblastien erilaistumiseen tutkittiin soluviljelmämallissa ja määritettiin kliinisessä potilastyössä paikallisesti käytettävän klodronaattiliuoksen pitoisuus. Lopuksi potilastyössä selvitettiin paikallisen klodronaattihuuhtelun ja suun kautta annostellun klodronaatin vaikutus proteesia ympäröivän luun tiheyteen ja proteesin kiinnittymiseen ympäristöönsä. Tutkimukseen valitut COX-estäjät vähensivät ihmisen kantasolujen erilaistumista osteoblasteiksi ja lisäsivät erilaistumista rasvasoluiksi. Lisäksi todettiin, että AppCCl2p estää mitokondrioissa tapahtuvaa hengitystä estämällä ADP/ATP-vaihtajan toiminnan, saaden aikaan solukuoleman. Vertailtaessa bisfosfonaatteja, tsoledronaatilla vaikutti olevan sekä ensimmäisen, että kolmannen polven (sisältää typpi-ryhmän) bispfosfonaattien vaikutuksia, joten tsoledronaatti kuuluu aivan uuteen bisfosfonaattiryhmään. Potilastutkimuksessa suun kautta ja paikallisesti reisiluun ytimeen annostellulla klodronaatilla oli täysin erilainen vaikutus. Suun kautta syötynä klodronaatti hidasti proteesin kiinnittymistä ja aiheutti osteolyysiä. Sen sijaan paikallinen klodronaatti nopeutti merkittävästi proteesin kiinnittymistä ympäröivään luuhun. Näiden tutkimustulosten perusteella voidaan olettaa, että COX-estäjät, samoin kuin peroraalinen bisfosfonaatti, voivat tahattomasti häiritä luun remodelaatiota
Feng, Jian. "Effect of redox potential, sulfide ions and a persulfide forming cysteine residue on carbon monoxide dehydrogenase." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/2197.
Повний текст джерелаTalungchit, Supitcha. "Enhancing resin-dentin bond effectiveness and durability: the role of ethanol-wet bonding technique, MMP-inhibition (chlorhexidine), and photoinitiator systems." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/2996.
Повний текст джерелаBrowne, Andrew. "The effects and regulation of the Wnt inhibitor Dickkopf-1 and the mechanistic target of rapamycin in osteotropic cancers." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-228981.
Повний текст джерелаPacios, Pujadó Sandra. "Cellular Mechanisms that affect Periodontal Destruction induced by Bacteria Infection in Diabetic and Non Diabetic Rats." Doctoral thesis, Universitat Internacional de Catalunya, 2014. http://hdl.handle.net/10803/275965.
Повний текст джерелаEl objetivo de este estudio fue evaluar la respuesta histológica y celular a la infección por A.actinomycetemcomitans (A.a) y como la diabetes exacerba la producción de TNF- α y la apoptosis que contribuye a la progresión de la enfermedad periodontal y al acoplamiento del hueso. Los resultados enlazan la infección de A. a con características importantes de destrucción periodontal y ofrece una nueva visión de cómo la diabetes agrava la destrucción periodontal con A. a mediante un aumento significativo de la respuesta inflamatoria, lo que lleva al aumento de pérdida ósea y produce un aumento de apoptosis en el epitelio gingival y en las células del tejido conectivo a través de un mecanismo de caspasa-3 dependiente. Los antibióticos tuvieron un efecto más pronunciado en mucho de los parámetros evaluados en las ratas diabéticas que en las normoglucémicas, sugiriendo una deficiencia en la capacidad de los animales diabéticos en combatir la infección. Además la diabetes prolonga la inflamación y la osteoclastogénesis en la periodontitis y a través de TNF limita el proceso normal de reparación modulando negativamente factores que regulan el hueso.
Lin, Tzu-Yin. "The world according to mast cells – the role of Kit in normal and neoplastic canine mast cells." The Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1189098916.
Повний текст джерелаDiffer, Christopher. "Taking NO for an answer: NO modulation of BMP2 signalling and osteoinduction (English)." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19599.
Повний текст джерелаBone Morphogenetic Protein 2 (BMP2) is a TGF-beta superfamily member, with a major focus on osteogenic activity and application in fracture healing. In order to improve efficiency of BMP2 in the clinic, it is assumed that additional, yet unknown compounds can improve BMP2 signalling and osteogenic activity. The Nitric Oxide (NO) pathway has previously shown to be connected with the BMP2 pathway in an endothelial context. Therefore, it was the aim of this study to unravel connections between the NO and BMP2 pathway in regulating BMP2 mediated signalling and osteoinduction. This was carried out through the application of inhibitors (LNAME, ODQ and LY83583) and activators (L-Arginine, Deta NONOate, SNAP and YC-1) of the NO pathway in combination with BMP2. A proposed connection between BMP2 and NO pathways via a Protein Kinase A (PKA) bridge was investigated by application of H89 inhibitor. In summary, these results show that the NO pathway can modulate BMP2 mediated signalling and osteoinductive activity. The PKA bridge connects NO and BMP2 only for the process of BMP2 signalling, but not for BMP2 mediated osteoinduction.
Engdahl, Cecilia. "Selective inhibition of acetylcholinesterase 1 from disease-transmitting mosquitoes : design and development of new insecticides for vector control." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-134625.
Повний текст джерелаIshak, Ramzi. "Protection of carbon anode against air burning : a new approach to apply and understand the inhibiting effect of boron impregnation." Doctoral thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/29953.
Повний текст джерелаAluminum electrolysis is a process that consumes energy and resources (raw materials, qualified personnel, time, etc.). Several research projects are underway around the world to improve the efficiency of the aluminum manufacturing process, to reduce toxic gas emissions (CO2, CO, CF4, C2F6 ...) and to reduce production costs. One of the current problems of alumina electrolysis is the excessive consumption of carbon anodes. Indeed, these anodes, when they are heated at high temperatures, are attacked by ambient air between 400 and 600 °C, and by the CO2 at 960 °C which results in an over-consumption of carbon, thereby reducing the manufacturing capacity of metallic aluminum per kg of carbon consumed. Currently, the average lifetime of an anode is between 20 and 30 days. The objective of this project is to reduce the reaction rate of anode oxidation under ambient air. Different methods have been developed to obtain an effective and economical protection which would reduce the over-consumption of the carbon anode against the phenomenon of air oxidation. Since boron oxide is known as an inhibitor of carbon/oxygen reaction, several attempts have been made to make a coating on the anode, confirming the inhibitory effect of boron oxide on this reaction, thus allowing protection of the carbon anodes. The influence of each of the parameters (temperature, concentration, duration of impregnation in the solution, etc.) were studied, as well. X-ray tomography showed that the anode is mainly attacked on the surface and that the boron oxide coating creates a physical barrier preventing access of oxygen to the anode. Further studies have been carried out to understand the inhibitor mechanism of boron oxide on carbon-oxygen reaction. According to the literature, boron oxide and boric acid can act in two ways: either by fixing on the anode surface resulting in blocking the active carbon sites or by creating a vitreous layer which serves as a physical barrier to oxygen. A kinetic study has been established which confirms that the number of interactions between oxygen and carbon sites decreases in the presence of boron. ToF-SIMS has revealed that boron is present as an oxide on the anode surface and also in the form of carbon-boron bond (BC-). Therefore, this acts like a chemical protection while boron atoms block the carbon active sites, preventing oxidation. The consumption of the carbon anode in the electrolysis cells is controlled by the impurities and the graphitization level as well as the mass transport through its porous structure. The impregnation of coke particle could have an effect on the porosity and its distribution. Coke particles (from 4000 μm to 4 760 μm in diameter) was impregnated with boron oxide in order to reveal its effect on the porosity. The specific surface area and the volumes of 3 conversion rates of particles (at 0, 15 and 35%) were determined by argon adsorption and mercury infiltration in order to evaluate the contributions of subcritical gasification on the total gasification of the anodes under air at 525 °C. To determine the critical pore size (TC) for the treated and untreated coke, the measurement of internal and external contributions of pores was used. It was revealed that the pore sizes of 0.1-10 μm and larger were the most active pores for the gasification under air. In addition, the volume of only very small pores (0.0004-0.001 μm) was slightly decreased by boron impregnation. However, the contribution of the size range of these small pores to anode gasification is negligible. In this thesis, a new method for the protection of anodes by boron oxide has been developed. This involves treating the raw materials before anode is formed by using a low concentration of boron oxide (in ppm) in order to limit the level of impurities contained in the produced metal. The results performed with standard equipment showed that the air reactivity of the anode decreased by 15%, the dusting by 90% and CO2/CO loss by 30%. The electrical resistivity of the anode was not affected by boron oxide at this low level. The influence of each of the parameters (temperature, concentration, etc.) on anode protection was optimized, as well.
Sharmin, Nahid. "Therapeutic Targeting of BMP and TGF-β Signalling Pathways for the Resolution of Pulmonary Arterial Hypertension". Thesis, University of Bradford, 2018. http://hdl.handle.net/10454/17177.
Повний текст джерелаCommonwealth Scholarship Commission in the UK
The full text will be available at the end of the embargo period, 31st July 2024.
El-Khassawna, Thaqif. "Cellular and molecular analysis of fracture healing in a neurofibromatosis type 1 conditional knockout mice model." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2013. http://dx.doi.org/10.18452/16781.
Повний текст джерелаNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease resulting from inactivating mutations in the gene encoding the protein neurofibromin. NF1 patients – around 50% – have abnormalities of the skeleton. Long bones are often affected, and the clinical signs range from tibial bowing to spontaneous fractures and even non-unions. Moreover, NF1 mice models could provide the understanding of the cell types involved in the resulting non-union and their behavior. This study analyzed the healing progress of femur fractures in a model of NF1 long bone dysplasia. Fracture callus was assessed at days 7, 10, 14, and 21 by µCT, histology, biomechanics, and molecular analyses. Bone healing was impaired in Nf1Prx1 mice femoral fracture. Results revealed increased periosteal bone deposition at the early stages of healing, decreased but persistent cartilage formation concomitant with fibrous tissue accumulation within the fracture site, decreased torsional stiffness, decreased bone mineral density, and increased fibrous tissue infiltration in the callus of mutant mice. This fibrous tissue accumulation hindered bone fracture healing, and was deposited by alpha smooth muscle actin-positive myofibroblasts, which were derived from a yet unidentified muscle fascia. This is further supported by the microarray analysis of callus tissues showing that genes crucial to muscle cells physiology, proliferation and differentiation were affected. In addition, extracellular matrix related genes were up-regulated in the mutants. In summary, this study shows a resemblance in the healing progression to the Nf1Prx1 mice model and NF1 patients, thereby, confirming the suitability of this mice model to explore the mechanism by which mutations in NF1 lead to non-unions. Moreover, in vitro and in vivo pilot assessments of MEK inhibitor treatment demonstrated a potential remedy for the lack of neurofibromin in bone healing.